ArticleScientific reports2016
Dimethyl fumarate blocks pro-inflammatory cytokine production via inhibition of TLR induced M1 and K63 ubiquitin chain formation.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
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Who cites it
54 citing papers in PubMed, 107 citations in OpenAlex.
- Itaconation and Succination as Metabolite-Derived Cysteine Modifications in Inflammatory Signalling: Biochemical Mechanisms, Chemoproteomic Mapping, and Therapeutic Opportunities.Cell biochemistry and biophysics · 2026Review
- Ivangustin, a sesquiterpene lactone from Inula japonica Thunb., attenuates neuroinflammation through covalent inhibition of ubiquitin-conjugating enzyme UBE2L3.Chinese medicine · 2026Article
- Fumarate and fumarate hydratase: an immunometabolite regulator of inflammation and diseases.Frontiers in immunology · 2026Review
- Fumarate Signaling in Cardiovascular Disease: Therapeutic Potential and Pathologic Pitfalls of DMF/MMF and FH1 Deficiency.Journal of cardiovascular translational research · 2025Review
- Unlocking Novel Therapeutic Potential of Angiotensin II Receptor Blockers.International journal of molecular sciences · 2025Review
- Exogenous pyruvate is therapeutic against colitis by targeting cytosolic phospholipase A2.Genes & diseases · 2025Article
- Mitochondria reactive oxygen species signaling-dependent immune responses in macrophages and T cells.Immunity · 2025Review
- Dimethyl Fumarate Attenuates Cyclophosphamide-Induced Bladder Damage and Enhances Cytotoxic Activity Against SH-SY5Y Cells.Journal of biochemical and molecular toxicology · 2025Article
- Nrf2-Independent Anti-Inflammatory Effects of Dimethyl Fumarate: Challenges and Prospects in Developing Electrophilic Nrf2 Activators for Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2024Review
- Review
- Dimethyl Fumarate-Loaded Gellan Gum Hydrogels Can Reduce In Vitro Chemokine Expression in Oral Cells.International journal of molecular sciences · 2024Article
- Regulation of proteostasis and innate immunity via mitochondria-nuclear communication.The Journal of cell biology · 2024Review
- Tuning the Reactivity of Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Activators for OptimalACS medicinal chemistry letters · 2023Article
- Dimethyl fumarate modulates the dystrophic disease program following short-term treatment.JCI insight · 2023Article
- Metabolic response to CNS infection with flaviviruses.Journal of neuroinflammation · 2023Review
- Article
- Novel potential pharmacological applications of dimethyl fumarate-an overview and update.Frontiers in pharmacology · 2023Review
- Review
- NAC, NAC, Knockin' on Heaven's door: Interpreting the mechanism of action of N-acetylcysteine in tumor and immune cells.Redox biology · 2022Review
- Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Dimethyl fumarate (DMF) possesses anti-inflammatory properties and is approved for the treatment of psoriasis and multiple sclerosis. While clinically effective, its molecular target has remained elusive - although it is known to activate anti-oxidant pathways. We find that DMF inhibits pro-inflammatory cytokine production in response to TLR agonists independently of the Nrf2-Keap1 anti-oxidant pathway. Instead we show that DMF can inhibit the E2 conjugating enzymes involved in K63 and M1 polyubiquitin chain formation both in vitro and in cells. The formation of K63 and M1 chains is required to link TLR activation to downstream signaling, and consistent with the block in K63 and/or M1 chain formation, DMF inhibits NFκB and ERK1/2 activation, resulting in a loss of pro-inflammatory cytokine production. Together these results reveal a new molecular target for DMF and show that a clinically approved drug inhibits M1 and K63 chain formation in TLR induced signaling complexes. Selective targeting of E2s may therefore be a viable strategy for autoimmunity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.